1. Field of the Invention
Paramagnetic species are commonly employed as shift or contrast reagents in nuclear magnetic resonance (NMR) studies. In clinical applications, these species are employed to alter magnetic properties in target tissue to enhance contrast and specificity in NMR imaging (MRI) and to improve spectrum resolution in NMR spectroscopy (MRS). Nacked paramagnetic species, however, are generally of limited clinical relevance in spectroscopic and imaging procedures, owing to their toxicity.
2. Discussion of Related Art
In order to exploit shift and contrast effects of these paramagnetic species in clinical diagnostic procedures, paramagnetic ions such as lanthanides, Fe.sup.3+, Cr.sup.3+, or Mn.sup.2+ are typically chelated with one or more identical ligands W to form simple complexes of the type MW.sub.x, wherein x is.gtoreq.1. Typical ligands W include bidentate and polydentate ligands such as polyphosphates, especially tripolyphosphate (PPP) and aminepolycarboxylates such as nitrilotriacetate (NTA), ethylenediaminetetraacetate (EDTA), and diethylenetriaminepentaacetate (DTPA). The complexes are structured according to their intended function: For example, [Dy(PPP).sub.2 ].sup.7- is a good shift reagent for sodium spectroscopy as the favorable geometry of Na.sup.+ relative to the paramagnetic dysprosium ion [Dy(III)] bound to the highly charged tripolyphosphate ligand induces large chemical shifts of the sodium ion; analogously, Gd(III) complexed with PPP to form [Gd(PPP).sub.2 ].sup.7- is an effective contrast agent for proton and sodium imaging.
Unfortunately, many of these simple complexes MW.sub.x known in the art have limited clinical utility. In the case of aminepolycarboxylate ligands, the paramagnetic complexes are typically only effective as contrast reagents in sodium imaging at relatively high and potentially toxic concentrations, probably owing to weak binding of Na.sup.+ or unfavorable geometry of the complex. The tripolyphosphate paramagnetic complexes MW.sub.x are effective at acceptably low concentrations, but the ligand is degraded in brain and muscle tissue, most likely by the action of pyrophosphatase, with resultant deposition of a potentially toxic paramagnetic ion in the tissue.